Trophoblast-derived tumor necrosis factor-alpha induces release of human chorionic gonadotropin using interleukin-6 (IL-6) and IL-6-receptor-dependent system in the normal human trophoblasts
| Autor: | K Yone, K. Masuhiro, Noboru Matsuzaki, Fumitaka Saji, Takeshi Taniguchi, Y. Li, Takashi Kameda, O. Tanizawa |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class Endocrinology Diabetes and Metabolism Clinical Biochemistry Alpha (ethology) Biology Monoclonal antibody Chorionic Gonadotropin Biochemistry Human chorionic gonadotropin Endocrinology Reference Values Internal medicine Placenta medicine Humans Receptors Immunologic reproductive and urinary physiology Interleukin-6 Tumor Necrosis Factor-alpha Biochemistry (medical) Antibodies Monoclonal Interleukin Trophoblast Drug Synergism Receptors Interleukin-6 Recombinant Proteins Trophoblasts medicine.anatomical_structure embryonic structures Interleukin-6 receptor Tumor necrosis factor alpha Interleukin-1 |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 74:184-191 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jcem.74.1.1727819 |
| Popis: | The titer of tumor necrosis factor-alpha (TNF alpha) secreted by placental blocks was determined by enzyme immunoassay. The source of placental TNF alpha was immunohistochemically demonstrated with monoclonal anti-TNF alpha antibody to be only trophoblasts. Purified trophoblasts produced 174.4 ng/L TNF alpha by 24 h of culture in vitro. To investigate the role of TNF alpha in placental hormonogenesis, purified trophoblasts were stimulated with recombinant TNF alpha (rTNF alpha) to determine the hCG titer by enzyme immunoassay. Trophoblasts stimulated with rTNF alpha released hCG in a dose-dependent fashion with kinetics similar to those of recombinant interleukin-1 (rIL-1)-stimulated trophoblasts. The stimulated trophoblasts released IL-6 before hCG, but failed to show hCG release when pretreated with anti-IL-6 receptor (anti-IL-6-R) monoclonal antibody PM-1. However, the pretreatment of trophoblasts with PM-1 did not interfere with rTNF alpha-induced IL-6 release, ruling out the possibility of a nonspecific toxic effect of PM-1 on trophoblasts. These results suggest that trophoblast-derived TNF alpha induced IL-6 release and then activated the IL-6-R system in trophoblasts to release hCG. Since IL-1 has also been demonstrated to induce similar release of IL-6 and hCG from trophoblasts, the effects of TNF alpha and IL-1 on these trophoblast functions were also examined. Simultaneous stimulation of trophoblasts with rTNF alpha and gamma IL-1 alpha resulted in synergistic enhancement of IL-6 release, subsequently leading to enhanced hCG release. Collectively, trophoblast-derived TNF alpha and IL-1 synergistically regulated the level of IL-6 secreted by trophoblasts, the magnitude of which determined the level of hCG released by activating the IL-6-R system in trophoblasts. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|